IL-12 COMPOSITIONS AND METHODS OF USE IN HEMATOPOIETIC RECOVERY
Aspects and embodiments of the instant disclosure provide therapeutic methods and compositions comprising interleukin 12 (IL-12) useful for improving hematopoietic recovery HSCT transplantation in a subject. In particular, the instant disclosure provide exemplary methods and compositions comprising IL-12 promoted hematopoiesis and increased the recovery of peripheral blood cells and survival in lethally irradiated mice as effectively as a BMCT, indicating that rHuIL-12 therapy can to increase HSC engraftment following HSCT. We identified IL-12Rβ2 expressing cells in irradiated mouse bone marrow which are potential targets of IL-12. Administration of rMuIL-12 increased the number of IL-12R□2 expressing Lin− cells in mouse bone marrow, indicating that bone marrow HSCs and niche cells are the direct target of rMuIL-12 and that hematopoiesis-promoting activity of rMuIL-12 is mediated by IL-12 receptors on HSCs. Finally, we show expression of IL-12β2 on human bone marrow lin− and CD34+ cells, indicating a potential role for IL-12 in human transplantation.
1 . A method of restoring hematopoiesis and reducing infectious complications comprising administering one or more effective dose(s) of IL-12 following myeloablative therapy.
2 . A method of restoring hematopoiesis and reducing infectious complications comprising administering one or more effective dose(s) of IL-12 prior to myeloablative therapy.
3 . (canceled)
4 . The method of claim 1 , where radiation therapy is used in the myeloablative therapy.
5 . The method of claim 1 , where chemotherapy is used in the myeloablative therapy.
6 . The method of claim 1 , wherein hematopoiesis is restored via an increased number of progenitor cells in the bone marrow.
7 - 12 . (canceled)
13 . A method for restoring hematopoiesis comprising administering one or more effective dose(s) of IL-12 either before, after, or before and after myeloablative therapy, wherein hematopoiesis is restored via activation of the IL-12 receptor on hematopoietic cells in the bone marrow.
14 . The method of claim 13 , wherein the hematopoietic cells comprise niche cells and stem cells.
15 . The method of claim 14 , wherein the niche cells comprise osteoblasts.
16 . The method of claim 13 , where hematopoiesis is restored following activation of the IL-12 receptor on megakaryocytes.
17 . (canceled)
18 . The method of claim 13 , wherein hematopoiesis is restored following activation of the IL-12 receptor on osteoblastic cells, megakaryocyte cells, and hematopoietic stem cells in the bone marrow.
19 . (canceled)
20 . The method of claim 1 , wherein the myeloablative therapy is followed by an autologous transplant.
21 . The method of claim 1 , wherein the myeloablative therapy is followed by an allogenic transplant.
22 . The method of claim 1 , wherein mobilization and collection of hematopoietic stem cells is done prior to myeloablative therapy.
23 . The method of claim 22 , wherein mobilization and collection of hematopoietic stem cells yields a low count of CD34+ cells.
24 . (canceled)
25 . The method of claim 1 , wherein the myeloablative therapy is given to treat a hematopoietic malignancy selected from the group consisting of chronic myeloid leukemia, chronic lymphocytic leukemia, mantle cell lymphoma, low-grade non-Hodgkin's lymphoma, acute myeloid leukemia, intermediate grade lymphoma, multiple myeloma, myelodysplastic syndrome and Hodgkin's disease.
26 . (canceled)
27 . The method of claim 1 , wherein the IL-12 is a recombinant human IL-12.
28 . The method of claim 1 , wherein the myeloablative method is a combination of radiation therapy and chemotherapy.
29 . The method of claim 1 , wherein the method comprises a non-myeloablative method.
30 . The method of claim 29 , wherein the non-myeloablative method comprises mini-transplant.
31 . The method of claim 29 , wherein the non-myeloablative method comprises reduced intensity conditioning (RIC).